Xaliproden - Sanofi-Synthelabo Inc.

Company Declines to Apply to FDAFall 2002

Sanofi-Synthelabo has decided to withdraw its application for the regulatory approval of the neurotrophic agent, xaliproden, for the treatment of amyotrophic lateral sclerosis (ALS) in the European Union. The application, which was based on two Phase III placebo-controlled trials, was filed in July 2001.

As previously communicated, the results of the two pivotal clinical trials of xaliproden (SR 57746A) 1 or 2mg in ALS patients treated with xaliproden in monotherapy and with riluzole, have shown that the compound is well tolerated, has a positive effect on pulmonary function and favorable trends on survival (time to permanent assisted ventilation, tracheostomy or death). However, the interpretation of the positive effect on pulmonary function, seen primarily in the monotherapy study, is complicated by the extent of the survival benefit that was smaller than the studies were powered to detect.

These results were not considered sufficiently robust to meet regulatory requirements for approval.

Sanofi-Synthelabo will continue to provide xaliproden to ALS patients treated in ongoing long-term extension studies in Europe and throughout the world, in accordance with the protocol and procedures defined by the national regulatory authorities.

Xaliproden is currently in clinical development in other indications such as Alzheimer dementia and peripheral neuropathy induced by antimitotic drugs.

Background

In the fall of 2000, Sanofi-Synthelabo released its preliminary analysis of data from two clinical trials of the compound, xaliproden, being studied for the treatment of amyotrophic lateral sclerosis.

The results of the two clinical trials of xaliproden were not conclusively positive. However, the preliminary results demonstrated strong trends that encouraged the study's Steering Committee to recommend that future studies be planned to achieve conclusive evidence regarding whether there is a treatment benefit of xaliproden in ALS.

As described in the press release on Sanofi-Synthelabo's web site "…the compound is well tolerated, has a positive effect on pulmonary function resulting in favorable trends on survival (time to permanent assisted ventilation, tracheotomy or death) as well as a positive effect on parameters related to the rate of progression of the disease."

In 1997, Sanofi initiated two randomized, double blind, placebo-controlled trials of its compound Xaliproden. These Phase III clinical trials evaluated the effectiveness, safety and tolerability of two doses of Xaliproden in patients with ALS at 54 investigational centers in North America and Europe. One study included 1200 patients who took the approved, marketed drug RiluzoleŽ and the other study included 800 patients not taking this drug.

All those patients taking part in the trial of Xaliproden, whether receiving the drug or the placebo, were studied for a period of 18 months. The trial was completed in early 2000 and a preliminary analysis of the data is complete.

Sanofi is a French multi-national health care corporation dedicated to developing novel and innovative therapeutic agents for a wide range of clinical disorders. Xaliproden is an original Sanofi compound which exhibits neurotrophic and neuroprotective effects. It is being developed primarily as a potential treatment for ALS.

Xaliproden is a nonpeptide compound that possesses neurotrophin-like activity. The compound reduces the histological (tissue), neurochemical and functional deficiencies produced in widely divergent models of experimental neurodegeneration. The ability of Xaliproden to increase the innervation of human muscle cells by spinal cord explants and to prolong the survival of mice suffering from progressive motor neuronopathy suggests the compound might be an effective therapy for the treatment of ALS. Even though the mechanism by which Xaliproden produces its neurotrophic and neuroprotective effects is not fully understood, it is thought to be related to the compound's ability to mimic the activity or stimulate the biosynthesis of a number of neurotrophins (such as NGF and BDNF) originating within the body.

For further information, please call James Fusilli, Sanofi at (212) 551-4314.